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Relation of body fat indexes to vitamin D status and deficiency among obese adolescents. Lenders CM, Feldman HA, Von Scheven E, Merewood A, Sweeney C, Wilson DM, Lee PD, Abrams SH, Gitelman SE, Wertz MS, Klish WJ, Taylor GA, Chen TC, Holick MF; Elizabeth Glaser Pediatric Research Network Obesity Study Group. Am J Clin Nutr. 2009 Sep;90(3):459-67. Epub 2009 Jul 29. PMID: 19640956 RESULTS: The mean (+/-SD) age of the adolescents was 14.9 +/- 1.4 y; 38 (66%) were female, and 8 (14%) were black. The mean (+/-SD) body mass index (in kg/m(2)) was 36 +/- 5, FM was 40.0 +/- 5.5%, and VAT was 12.4 +/- 4.3%. Seventeen of the adolescents were vitamin D deficient, but none had elevated PTH concentrations. Bone mineral content and bone mineral density were within 2 SDs of national standards. In a multivariate analysis, 25(OH)D decreased by 0.46 +/- 0.22 ng/mL per 1% increment in FM (beta +/- SE, P = 0.05), whereas PTH decreased by 0.78 +/- 0.29 pg/mL per 1% increment in VAT (P = 0.01). CONCLUSIONS: To the best of our knowledge, our results show for the first time that obese adolescents with 25(OH)D deficiency, but without elevated PTH concentrations, have a bone mass within the range of national standards (+/-2 SD). The findings provide initial evidence that the distribution of fat may be associated with vitamin D status, but this relation may be dependent on metabolic factors

Parathyroid hormone, but not vitamin D, is associated with the metabolic syndrome in morbidly obese women and men: a cross-sectional study. Hjelmesaeth J, Hofsø D, Aasheim ET, Jenssen T, Moan J, Hager H, Røislien J, Bollerslev J. Cardiovasc Diabetol. 2009 Feb 3;8:7. PMID: 19187564 doi:10.1186/1475-2840-8-7 CONCLUSION: The PTH level, but not the vitamin D level, is an independent predictor of MS in treatment seeking morbidly obese Caucasian women and men. Randomized controlled clinical trials, including different therapeutic strategies to lower PTH, e.g. calcium/vitamin D supplementation and weight reduction, are necessary to explore any cause-and-effect relationship.

Plasma calcidiol, season, and serum parathyroid hormone concentrations in healthy elderly men and women. Dawson-Hughes B, Harris SS, Dallal GE. Am J Clin Nutr. 1997 Jan;65(1):67-71. PMID: 8988915 Plasma calcidiol and serum PTH concentrations were inversely related, with PTH rising slowly as calcidiol concentrations declined below 110 nmol/L (95 CI: 60, 168 nmol/L). More than 90% of the men and women had calcidiol concentrations below this value in the wintertime. The high prevalence of lower wintertime calcidiol values may increase risk of bone loss in elderly men and women.

Kalsiumaineenvaihdunnan häiriöt ilmenevät hyper- tai hypokalsemiana, hyperkalsiuriana tai luuston aineenvaihduntahäiriöinä (osteoporoosi, osteomalasia, riisitauti, renaalinen osteodystrofia, Pagetin tauti). Epäiltäessä kalsiumaineenvaihdunnan häiriöitä voidaan käyttää seuraavanlaisia tutkimuksia: seerumin ja virtsan kalsium, seerumin ionosoitu kalsium, seerumin fosfaatti, albumiini, alkaalinen fosfataasi ja tarvittaessa sen isoentsyymit, kreatiniini, kloridi ja PTH. PTH:sta on mahdollista määrittää intakti PTH sekä sen keskimolekyyli- ja N-terminaalifragmentti. Luun aineenvaihdunnan biokemiallisia mittareita voidaan käyttää kuvantamaan luun hajoamista ja/tai rakentumista. Luun rakentumisen seerumimarkkereita ovat osteokalsiini ja tyypin 1 prokollageenin aminoterminaalinen propeptidi (PINP). Vastaavasti luunhajoamista kuvastavat virtsan ja seerumin tyypin 1 kollageenin aminoterminaalinen telopeptidi (NTx) sekä seerumin tartraattiresistentti alkalinen fosfataasi (TRAP). Luuston tilaa voidaan selvittää röntgenologisesti natiivikuvin (destruktiot, murtumat ja valemurtumat, resorptio- ja osteoskleroosipesäkkeet). Luun mineraalipitoisuuden määrittämisessä käytetään tiheysmittareita. Koepalan otto luustosta tulee kyseeseen erikoistilanteissa histologisen diagnoosin saamiseksi. Hyperkalsemia Hyperkalsemia on monasti sattumalöydös varsin vähäoireisella epämääräisiä vaivoja valittavalla potilaalla. Tavallisimmat oireet on esitetty taulukossa 1. Tyypillinen hyperkalsemiapotilas on epämääräisistä neuropsykiatrisista oireista kärsivä henkilö. Aikaisemmin tyypilliset munuaiskivipotilaat ovat jäämässä selvään vähemmistöön. Vanhuksilla hyperkalsemia voi aiheuttaa dementian kaltaisen sekavuustilan. Mikäli S-Ca on alle 3 mmol/l, voidaan potilas tutkia rauhassa polikliinisesti. Mikäli arvo sen sijaan on selvästi yli 3 mmol/l ja se vielä nousee perättäisissä mittauksissa, on tutkimuksia kiirehdittävä. Kalsiumarvon

25-Hydroxyvitamin D and functional outcomes in adolescents. Lamberg-Allardt CJ, Viljakainen HT. Am J Clin Nutr. 2008 Aug;88(2):534S-536S. Review. PMID: 18689396 CONCLUSIONS Cross-sectional studies have shown a relation among serum 25(OH)D concentration, serum PTH concentration, and BMD in adolescents. Long-term randomized controlled intervention studies have shown that vitamin D3 supplementation has a positive effect on BMD in adolescence; some of these studies found an effect with doses as small as 5 µg (200 IU) to 10 µg (400 IU) per day, or without supplemental calcium.

Healthy elderly French women living at home have secondary hyperparathyroidism and high bone turnover in winter. EPIDOS Study Group. Chapuy MC, Schott AM, Garnero P, Hans D, Delmas PD, Meunier PJ. J Clin Endocrinol Metab. 1996 Mar;81(3):1129-33. PMID: 8772587 These results show that vitamin D status of a French aged population in good health and living at home depends mainly on lifestyle. Like institutionalized women, old women living at home exhibit clear evidence of senile hyperparathyroidism in the winter, secondary in part to a reduced 25OHD level and associated with biological signs of increased bone turnover. The maintenance of PTH within the normal range for healthy adults by vitamin D and calcium treatment might constitute an approach for the prevention of bone loss in the entire

Randomized comparison of the effects of the vitamin D3 adequate intake versus 100 mcg (4000 IU) per day on biochemical responses and the wellbeing of patients. Vieth R, Kimball S, Hu A, Walfish PG. Nutr J. 2004 Jul 19;3:8. PMID: 15260882 doi:10.1186/1475-2891-3-8 CONCLUSION: The highest AI for vitamin D brought summertime 25(OH)D to >40 nmol/L, lowered PTH, and its use was associated with improved wellbeing. The 100 mcg/day dose produced greater responses. Since it was ethically necessary to provide a meaningful dose of vitamin D to these insufficient patients, we cannot rule out a placebo wellbeing response, particularly for those on the lower dose. This work confirms the safety and efficacy of both 15 and 100 mcg/day vitamin D3 in patients who needed additional vitamin D.

Improved cholecalciferol nutrition in rats is noncalcemic, suppresses parathyroid hormone and increases responsiveness to 1, 25-dihydroxycholecalciferol. Vieth R, Milojevic S, Peltekova V. J Nutr. 2000 Mar;130(3):578-84. PMID: 10702588 We conclude suppression of 1,25(OH)(2)D and PTH, and higher renal VDR mRNA and 24-hydroxylase did not involve higher free 1,25(OH)(2)D concentration or a first pass effect at the gut. Thus, 25(OH)D or a metabolite other than 1,25(OH)(2)D is a physiological, transcriptionally and biochemically active, noncalcemic vitamin D metabolite. When viewed from a perspective that starts with higher vitamin D nutrition, the results indicate that low vitamin D nutrition may bring about a form of resistance to 1,25(OH)2D. This situation would explain why, in humans, nutritional rickets and osteomalacia are commonly associated with normal or increased levels of 1,25(OH)2D (Chesney et al. 1981Citation , Eastwood et al. 1979Citation , Garabedian et al. 1983Citation ,Rasmussen et al. 1980Citation )-these are not like the low hormone levels associated with any other endocrine-deficiency disorder. A connection between lower vitamin D nutrition and vitamin D resistance helps to explain why the supposedly inactive compound 25(OH)D is more relevant in diagnosing nutritional rickets than is the active hormone 1,25(OH)2D. If the features of improved vitamin D nutrition shown here were demonstrated for any newly synthesized compound, the compound would be classified as a noncalcemic 1,25(OH)2D analogue (Brown et al. 1989Citation , Finch et al. 1999Citation , Goff et al. 1993Citation , Koshizuka et al. 1999Citation ). Thus, we contend that 25(OH)D or a metabolite of it other than 1,25(OH)2D exists as a physiological and biologically-active noncalcemic vitamin D metabolite whose effects require further examination, particularly in relationship to studies involving the synthetic analogs of 1,25(OH)2D.

Vitamin D is safe when used in physiological doses (those used by Nature). Physiological doses are 3,000-5,000 IU/day, from all sources (sun, diet and supplements). Should hypercalcemia occur with such doses, it is due to vitamin D hypersensitivity syndrome, not vitamin D toxicity. Vitamin D hypersensitivity syndromes include conditions such as primary hyperparathyroidism, occult cancers (especially lymphoma) or granulomatous disease (especially sarcoidosis). In such cases, treatment of vitamin D deficiency should be done under the care of a knowledgeable physician. A serum 25(OH)D, serum 1,25(OH)D, PTH and SMA will lead the clinician in the right direction.

Depression is associated with decreased 25-hydroxyvitamin D and increased parathyroid hormone levels in older adults. Hoogendijk WJ, Lips P, Dik MG, Deeg DJ, Beekman AT, Penninx BW. Arch Gen Psychiatry. 2008 May;65(5):508-12. PMID: 18458202 Conclusion The results of this large population-based study show an association of depression status and severity with decreased serum 25(OH)D levels and increased serum PTH levels in older individuals.

Serum 25-hydroxyvitamin D levels in vitamin D-insufficient hip fracture patients after supplementation with ergocalciferol and cholecalciferol. Glendenning P, Chew GT, Seymour HM, Gillett MJ, Goldswain PR, Inderjeeth CA, Vasikaran SD, Taranto M, Musk AA, Fraser WD. Bone. 2009 Nov;45(5):870-5. Epub 2009 Jul 23. PMID: 19631774 doi:10.1016/j.bone.2009.07.015 Cholecalciferol supplementation resulted in a 31% greater increase in total HPLC-measured 25OHD (p=0.010) and 52% greater rise in RIA-measured 25OHD (p0.05). In vitamin D-insufficient hip fracture patients, supplementation with cholecalciferol 1000 IU/day for three months was more effective in increasing serum 25OHD than an equivalent dose of ergocalciferol. However, the lack of difference in PTH lowering between calciferol treatments raises questions about the biological importance of this observation.

Prevalence of low serum vitamin D concentration in an urban population of elderly women in Poland. Napiórkowska L, Budlewski T, Jakubas-Kwiatkowska W, Hamzy V, Gozdowski D, Franek E. Pol Arch Med Wewn. 2009 Nov;119(11):699-703. PMID: 19920793 CONCLUSIONS: The prevalence of low vitamin D concentrations in an urban population of elderly women in Poland is very high. Lower vitamin D levels are associated with a higher PTH concentration

Effectiveness and safety of vitamin D in relation to bone health. Cranney A, Horsley T, O'Donnell S, Weiler H, Puil L, Ooi D, Atkinson S, Ward L, Moher D, Hanley D, Fang M, Yazdi F, Garritty C, Sampson M, Barrowman N, Tsertsvadze A, Mamaladze V. Evid Rep Technol Assess (Full Rep). 2007 Aug;(158):1-235. Review. PMID: 18088161 CONCLUSIONS: The results highlight the need for additional high quality studies in infants, children, premenopausal women, and diverse racial or ethnic groups. There was fair evidence from studies of an association between circulating 25(OH)D concentrations with some bone health outcomes (established rickets, PTH, falls, BMD). However, the evidence for an association was inconsistent for other outcomes (e.g., BMC in infants and fractures in adults). It was difficult to define specific thresholds of circulating 25(OH)D for optimal bone health due to the imprecision of different 25(OH)D assays. Standard reference preparations are needed so that serum 25(OH)D can be accurately and reliably measured, and validated. In most trials, the effects of vitamin D and calcium could not be separated. Vitamin D(3) (>700 IU/day) with calcium supplementation compared to placebo has a small beneficial effect on BMD, and reduces the risk of fractures and falls although benefit may be confined to specific subgroups. Vitamin D intake above current dietary reference intakes was not reported to be associated with an increased risk of adverse events. However, most trials of higher doses of vitamin D were not adequately designed to assess long-term harms.

Effectiveness and safety of vitamin D in relation to bone health. Cranney A, Horsley T, O'Donnell S, Weiler H, Puil L, Ooi D, Atkinson S, Ward L, Moher D, Hanley D, Fang M, Yazdi F, Garritty C, Sampson M, Barrowman N, Tsertsvadze A, Mamaladze V. Evid Rep Technol Assess (Full Rep). 2007 Aug;(158):1-235. Review. PMID: 18088161 CONCLUSIONS: The results highlight the need for additional high quality studies in infants, children, premenopausal women, and diverse racial or ethnic groups. There was fair evidence from studies of an association between circulating 25(OH)D concentrations with some bone health outcomes (established rickets, PTH, falls, BMD). However, the evidence for an association was inconsistent for other outcomes (e.g., BMC in infants and fractures in adults). It was difficult to define specific thresholds of circulating 25(OH)D for optimal bone health due to the imprecision of different 25(OH)D assays. Standard reference preparations are needed so that serum 25(OH)D can be accurately and reliably measured, and validated. In most trials, the effects of vitamin D and calcium could not be separated. Vitamin D(3) (>700 IU/day) with calcium supplementation compared to placebo has a small beneficial effect on BMD, and reduces the risk of fractures and falls although benefit may be confined to specific subgroups. Vitamin D intake above current dietary reference intakes was not reported to be associated with an increased risk of adverse events. However, most trials of higher doses of vitamin D were not adequately designed to assess long-term harms.

Dietary acid-base balance, bone resorption, and calcium excretion. Jajoo R, Song L, Rasmussen H, Harris SS, Dawson-Hughes B. J Am Coll Nutr. 2006 Jun;25(3):224-30. PMID: 16766781 Conclusions: Diet changes that increase renal NAE are associated with increases in serum PTH, bone resorption, and calcium excretion over a 60-day period.

A positive dose-response effect of vitamin D supplementation on site-specific bone mineral augmentation in adolescent girls: a double-blinded randomized placebo-controlled 1-year intervention. Viljakainen HT, Natri AM, Kärkkäinen M, Huttunen MM, Palssa A, Jakobsen J, Cashman KD, Mølgaard C, Lamberg-Allardt C. J Bone Miner Res. 2006 Jun;21(6):836-44. PMID: 16753014 doi: 10.1359/jbmr.060302 We conclude that the current vitamin D recommendation for adolescent girls, at least in the northern latitudes, is too low to ensure sufficient vitamin D status during winter. Intake of vitamin D at rates of 10-15 μg/day aids to maintain stable S-25(OH)D concentrations during winter. Vitamin D induced BMC augmentation by decreasing bone resorption, but not affecting bone formation, which was reflected by the biochemical markers of bone turnover. Optimizing bone mineral gain in adolescence is crucial to the prevention of osteoporosis later in life. Increasing vitamin D intake to 10-15 μg/day aids in attaining this goal.

Wintertime vitamin D supplementation inhibits seasonal variation of calcitropic hormones and maintains bone turnover in healthy men. Viljakainen HT, Väisänen M, Kemi V, Rikkonen T, Kröger H, Laitinen EK, Rita H, Lamberg-Allardt C. J Bone Miner Res. 2009 Feb;24(2):346-52. PMID: 18847321

Age-related changes in the 25-hydroxyvitamin D versus parathyroid hormone relationship suggest a different reason why older adults require more vitamin D. Vieth R, Ladak Y, Walfish PG. J Clin Endocrinol Metab. 2003 Jan;88(1):185-91. PMID: 12519850 This study shows that all age groups exhibit a high prevalence of 25(OH)D insufficiency and secondary hyperparathyroidism. Older adults are just as efficient in maintaining 25(OH)D, but they need more vitamin D to produce the higher 25(OH)D concentrations required to overcome the hyperparathyroidism associated with their diminishing renal function

An evaluation of the relative contributions of exposure to sunlight and of diet to the circulating concentrations of 25-hydroxyvitamin D in an elderly nursing home population in Boston. Webb AR, Pilbeam C, Hanafin N, Holick MF. Am J Clin Nutr. 1990 Jun;51(6):1075-81. PMID: 2349922

Vitamin D in preventive medicine: are we ignoring the evidence? Zittermann A. Br J Nutr. 2003 May;89(5):552-72. Review. PMID: 12720576 Vitamin D is metabolised by a hepatic 25-hydroxylase into 25-hydroxyvitamin D (25(OH)D) and by a renal 1alpha-hydroxylase into the vitamin D hormone calcitriol. Calcitriol receptors are present in more than thirty different tissues. Apart from the kidney, several tissues also possess the enzyme 1alpha-hydroxylase, which is able to use circulating 25(OH)D as a substrate. Serum levels of 25(OH)D are the best indicator to assess vitamin D deficiency, insufficiency, hypovitaminosis, adequacy, and toxicity. European children and young adults often have circulating 25(OH)D levels in the insufficiency range during wintertime. Elderly subjects have mean 25(OH)D levels in the insufficiency range throughout the year. In institutionalized subjects 25(OH)D levels are often in the deficiency range. There is now general agreement that a low vitamin D status is involved in the pathogenesis of osteoporosis. Moreover, vitamin D insufficiency can lead to a disturbed muscle function. Epidemiological data also indicate a low vitamin D status in tuberculosis, rheumatoid arthritis, multiple sclerosis, inflammatory bowel diseases, hypertension, and specific types of cancer. Some intervention trials have demonstrated that supplementation with vitamin D or its metabolites is able: (i) to reduce blood pressure in hypertensive patients; (ii) to improve blood glucose levels in diabetics; (iii) to improve symptoms of rheumatoid arthritis and multiple sclerosis. The oral dose necessary to achieve adequate serum 25(OH)D levels is probably much higher than the current recommendations of 5-15 microg/d.